Department of Medical Pharmacology, Marmara University Faculty of Medicine, Istanbul, Turkey; Brain Repair and Imaging in Neural Systems (B.R.A.I.N.S) Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Department of Medical Pharmacology, Marmara University Faculty of Medicine, Istanbul, Turkey; Epilepsy Research Centre (EPAM), Marmara University, Istanbul, Turkey.
Pharmacol Biochem Behav. 2022 Feb;213:173317. doi: 10.1016/j.pbb.2021.173317. Epub 2021 Dec 30.
Basal ganglia structures play an important role in the pathophysiology of absence epilepsy, known as remote control of absence seizures. We examined the role of the nigrostriatal dopaminergic pathway in absence epilepsy through behavioral and electroencephalography (EEG) parameters, immunohistochemical, and biochemical characteristics of dopamine and serotonin in the genetic absence epilepsy rat model.
The nigrostriatal pathway was degenerated by the injection of chemical 6-hydroxydopamine hydrobromide (6-OHDA) into the medial forebrain bundle (MFB) in Wistar and genetic absence epilepsy rats from Strasbourg (GAERS). On the 21st day after stereotaxic surgery, spike-and-wave discharges (SWDs) on EEG were recorded in GAERS groups. Thereafter, Wistar-Control, GAERS-Control, Wistar-6OHDA, GAERS-6OHDA rats were subjected to the cylinder and apomorphine-induced rotation tests. Dopaminergic or serotonergic immunoreactivity was examined in the cortex, striatum, and substantia nigra pars compacta. High-performance liquid chromatography method was used for biochemical analysis of dopamine and serotonin in the cortex and thalamus.
In behavioral analysis, the number of rotations in the GAERS-6OHDA group was significantly higher than in Wistar-6OHDA rats. The degeneration of the nigrostriatal dopaminergic pathway produced a significant increase in the cumulative duration of SWDs and the duration of each SWD in GAERS-6OHDA rats. GAERS-Control rats displayed significantly higher cortical and striatal serotonin immunoreactivity and cortical serotonin level compared to Wistar-Control animals. Moreover, cortical and striatal serotonin immunoreactivity and cortical serotonin levels increased in Wistar-6OHDA and GAERS-6OHDA groups compared to their control groups.
The effect of 6-OHDA-induced MFB lesion on absence epilepsy was examined for the first time by comparing Wistar and GAERS rats. The nigrostriatal dopaminergic pathway as a part of the remote-control system is likely to participate in the seizure network.
基底节结构在失神性癫痫的病理生理学中起着重要作用，被称为失神发作的远程控制。我们通过行为和脑电图（EEG）参数、多巴胺和 5-羟色胺的免疫组织化学和生化特征，研究了黑质纹状体多巴胺能通路在遗传性失神癫痫大鼠模型中的作用。
通过将化学物质 6-羟多巴胺氢溴酸盐（6-OHDA）注入内侧前脑束（MFB），使 Wistar 和来自斯特拉斯堡的遗传性失神癫痫大鼠（GAERS）的黑质纹状体通路退化。立体定向手术后第 21 天，在 GAERS 组记录 EEG 上的棘波和慢波放电（SWD）。此后，Wistar-Control、GAERS-Control、Wistar-6OHDA、GAERS-6OHDA 大鼠进行了圆筒和阿朴吗啡诱导的旋转测试。在皮质、纹状体和黑质致密部检查多巴胺能或 5-羟色胺能免疫反应性。使用高效液相色谱法对皮质和丘脑中的多巴胺和 5-羟色胺进行生化分析。
在行为分析中，GAERS-6OHDA 组的旋转次数明显高于 Wistar-6OHDA 大鼠。黑质纹状体多巴胺能通路的退化导致 GAERS-6OHDA 大鼠的 SWD 总持续时间和每个 SWD 的持续时间显著增加。GAERS-Control 大鼠的皮质和纹状体 5-羟色胺免疫反应性和皮质 5-羟色胺水平明显高于 Wistar-Control 动物。此外，与对照组相比，Wistar-6OHDA 和 GAERS-6OHDA 组的皮质和纹状体 5-羟色胺免疫反应性和皮质 5-羟色胺水平增加。
首次通过比较 Wistar 和 GAERS 大鼠，研究了 6-OHDA 诱导的 MFB 损伤对失神性癫痫的影响。黑质纹状体多巴胺能通路作为远程控制系统的一部分，可能参与了癫痫网络。
